PHARMACOLOGY OF [2-(OCTAHYDRO-1-AZOCINVL)-ETHYL-GUANIDINE SULFATE (SU-5864)

¹ Research Department, Ciba Pharmaceutical Products Inc., Summit, New Jersey

[2-(Octahydro-1-azocinyl)-ethyl]-guanidine sulfate (Su-5864) profoundly lowered the arterial pressure of unanesthetized neurogenic and renal hypertensive dogs. It had a slight hypotensive action in the normotensive unanesthetized and anesthetized dog. Su-5864 was likewise a potent antagonist to the pressure responses elicited by (1) bilateral occlusion of the carotid arteries and (2) injection of high doses of amphetamine. These actions lasted for periods ranging from 4 days to 3 weeks following single intravenous injections. The first several hours of Su-5864 action were characterized by strong sympathetic-like actions. During the remainder of the course of action of this drug sympathetic atony was prevalent. The nictitating membranes and the arterial system were unresponsive to stimulation of efferent sympathetic nerves. This prolonged period of unresponsiveness cannot be attributed to interference with the conduction of nerve impulses or transmission across ganglia since such effects are very transient. During the period when the nictitating membranes and arterial system were poorly responsive to nerve stimulation they were hyperresponsive to injected norepinephrine. It is concluded that Su-5864 chronically interferes with the release, and/or normal distribution subsequent to release, of the neurohumoral transmitter at the sympathetic neuromuscular junction.

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